The planned investigations will aim inquiring into the pathogenesis of the lesions of the disease cystic fibrosis (CF) with a view toward identifying the cell type affected in sweat glands of these patients. Studies will concentrate on examining explanted sweat glands by freeze-fracture, quantitative morphometry, and a range of cytochemical methods to demonstrate enzymes, electrolytes and cholinergic receptors. Inquiry is proceeding into pathogenetic mechanisms for development of abnormal megagranules in leukocytes, hepatocytes, renal tubules and other cells of beige mice with a disease analogous to the Chediak-Higashi syndrome of man. Differentiation of complex characterizing both the types of glycoprotien-rich secretion and the luminal glycocalyx in various epithelial cells of the stomach. A major approach will concern measurement of ion content in proximal and distal segments of explanted sweat glands and fluxes of sodium and other cations in these segments. New approaches to assaying CF factors in body fluids will be tested. Work on development and application of cytochemical methods for demonstrating complex carbohydrates, antigens and other components will continue.